The Effect of Lurasidone on Anxiety Symptoms in Patients With Bipolar Depression

Objective: To assess the effects of lurasidone on anxiety symptoms and sleep disruption, and their moderating and mediating roles on treatment response in bipolar depression. Methods:This post hoc analysis included pooled data from 2 previously published 6-week placebo-controlled trials of lurasidone for bipolar I depression conducted between April 2009 and February 2012.Hamilton Anxiety Rating Scale (HAM-A) "psychic anxiety" (items 1-6, 14) and "somatic anxiety" (items 7-13) subscores were calculated.Functional outcome was assessed by the Sheehan Disability Scale.Results: All subjects (n = 824) had at least 1 psychic anxiety and 729 (88.5%) had at least 1 somatic anxiety symptom at baseline.594 subjects (72.1%) experienced baseline sleep disturbance.Lurasidone, as monotherapy (20-60 mg/d and 80-120 mg/d pooled dose groups vs placebo) and adjunctive therapy (20 to 120 mg/d flexibly dosed vs placebo) with lithium or valproate, significantly reduced HAM-A psychic anxiety (-4.82 vs -2.97, P < .001,monotherapy; -5.56 vs -4.26, P = .009,adjunctive therapy) and somatic anxiety (-1.89 vs -1.37, P = .048,monotherapy; -2.22 vs -1.47, P = .006,adjunctive therapy) subcomponents.Improvement in anxiety symptoms mediated reduction in depressive symptoms and functional impairment.Decrease in sleep at baseline predicted change in anxiety symptoms with lurasidone treatment at week 6. Conclusions:Lurasidone was superior to placebo in reducing psychic and somatic anxiety in the short-term treatment of bipolar depression.Improvement in depressive symptoms and reduction in functional impairment were associated with reduction in anxiety symptoms moderated by baseline sleep disturbance during lurasidone treatment.Trial Registration: ClinicalTrials.